[Combined therapy with polyamine biosynthesis inhibitors and mitomycin C]

Abstract

An attempt was made to analyse tumor growth after cessation of combined therapy with the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), as well as mitomycin C (MMC). DFMO 1000 mg/kg, MGBG 50 mg/kg and/or MMC 2 mg/kg were given intraperitoneally to BALB/c nu/nu mice xenotransplanted human gastric cancer, and its growth as well as DNA biosynthesis were measured daily, after cessation of these combined treatments. Histological observation of the tumor was also performed by hematoxylin-eosin staining. The combination with DFMO and MGBG stunted tumor growth during the treatment, but 3 days later its growth and DNA biosynthesis were accelerated distinctly. MMC injection halted tumor growth, and 5 days after termination of MMC injection its growth rate and DNA biosynthesis almost completely recovered. The microscopic findings on the 4th day after termination of MMC injection were similar to those of DFMO + MGBG treatment. The combination DFMO, MGBG and MMC suppressed not only tumor growth during the treatment, but also tumor growth and DNA biosynthesis over 7 days. The histologic observation 4 days later revealed extensive damage.